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The study of how genes control development. Advances in the field have emphasized the degree of conservation of the genes controlling development throughout evolution. Thus, such distant organisms as insects and vertebrates share a number of very homologous genes controlling early development. For example, homeobox genes (Hox genes) are used in both insects and mammals to provide information for anterior-posterior positioning. The conservation of the genes is so great that the human version of a Hox gene can sometimes substitute for the mutant Drosophila gene and correct abnormalities of early development.
Most genes involved in sex determination have not been conserved, but a gene has been cloned in the nematode Caenorhabditis elegans which is highly homologous to a gene involved in the Drosphila sex determination cascade and to a gene in mammals whose role in sex determination has yet to be fully elucidated. Another organism which is elucidating these genes and has become of great interest is the zebrafish. Its small size and clear embryo allow easy screening of many developmental mutations, and many of the above-mentioned evolutionary conservations have been confirmed in the zebrafish.
Determination is a stage during the developmental process when genes become committed to a particular expression pattern leading to a differentiated state. At the time of this stage, the differentiated state is not yet visible. This aspect can be confirmed by transplantation of determined but not yet differentiated tissues to ectopic sites and observing the transplant's development. Advances have shown that some cell types are not as highly determined as was previously thought. Brain cells have given rise to blood cells, and bone marrow cells have given rise to bone and muscle. This apparent lack of determination in cells previously believed to be determined suggests greater potential for plasticity and the possibility of manipulating cells to new fates to create organs for human transplantation, for example.
Another area of research has involved maternal inheritance. Many of the genes responsible for the determination of cell fate in C. elegans larva are laid down in the egg; that is, they are maternal-effect genes. In this case, it is not the genotype of the zygote which influences development but that of the mother. Thus, homozygosity for a recessive mutation in the mother leads to altered development, even though the sperm is from a homozygous wild-type male and the resulting zygote was heterozygous. The percentage of maternal-effect genes is also high in Drosophila. See Gene action
Another general phenomenon under genetic control during development is induction—the action of one cell or tissue on other cells in order to determine altered gene expression in them.
Homoeotic mutations change one paired structure to another of a more interior or posterior compartment (for example, a leg to an antenna). The study of their structure and function has provided a paradigm for the role of genes in conveying positional information during development. In Drosophila, seven homoeotic genes are grouped in two complexes. Their role in establishing segmental identities is well defined, and the DNA sequence of the genes shows a highly conserved element called the homeobox. This conserved sequence is also found in some pair-rule and polarity genes, and the search for genes homologous to these led to the identification of other genes that are highly conserved in animal evolution. Although Drosophila uses one set of homeobox genes (separated into two clusters on two different chromosomes), mammals have amplified the set of genes to a minimum of four clusters of the size of the single cluster in Drosophila. These genes maintain the same patterns of expression in both mammals and Drosophila. They are expressed 5′ to 3′ in order of transcription, and the 5′-to-3′ order in the cluster is also reflected in the posterior-to-anterior limits of expression of the gene products. Most mutations in homeobox genes are recessive, and embryonic stem-cell knockouts have disclosed that, because there is sufficient redundancy in the mammalian homeobox clusters, the homozygous absence of one homeobox gene does not always result in an apparent phenotype. Paired box genes are another highly conserved family of genes, first identified for their important developmental roles in Drosophila. Mutations in these genes frequently cause dominantly inherited birth defects in mammals.
Imprinting, a developmentally important phenomenon that was first discovered in insects, is also important for mammalian development and human disease. In imprinting, genes transmitted through the testis sometimes function differently from those transmitted through the ovary. Many portions of the genome have been found to be imprinted, including the reciprocal imprinting of insulinlike growth factor and its receptor. Some major human diseases occur when both a paternal and a maternal copy of a gene are not present. The Prader-Willi syndrome, a disorder of mental retardation, poor appetite regulation, and mild dysmorphic features, is an example. Advances have strongly implicated gametogenesis-specific methylation of key controlling regions in the imprinting process. Such imprints seem to be erased from the migrating germ cells enroute to the developing gonad, and then are established differentially during ovigenesis and spermatogenesis, presumably by proteins uniquely expressed in the two different gonads and with specificity for the particular DNA sequences. The actual expression of imprinting differences frequently involves (1) competition between cis-linked genetic elements and (2) a nontranslated RNA species. See Developmental biology, Genetics